Physiological effects of inactivation and the roles of
            <i>Elovl3</i>
            /ELOVL3 in maintaining ocular homeostasis

Wilkerson, Amber; Bhat, Nita; Pham, Hoang Quoc Hai; Yüksel, Seher; Butovich, Igor A.

doi:10.1096/fj.202002323r

Cited by 8 publications

(15 citation statements)

References 58 publications

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“…In conclusion, inactivation of Soat1 confirmed its previously predicted critical role in meibogenesis [7,11,12,21,23] and led to an almost complete elimination of MG-derived CE and Chl-OAHFA ( Figure 9). This change in meibum caused dramatic shifts in the ocular phenotype of Soat1-ablated mice that resembled many features characteristic of human MGD.…”

Section: Discussionsupporting

confidence: 81%

“…Importantly, the makeup of CE in meibum demonstrated only subtle inter-donor variations in humans [12] and mice [21]. Recently, we reported that MG of humans highly expressed key genes of Chl biosynthesis, such as ACAT1/ACAT2, DHCR7, DHCR24, FDFT1, HMGCR, HMGCS1/HMGCS2, LSS, MSMO1, SQLE, and others, and so did MG of mice [7,11,12,23]. Genes that encode enzymes of CE biosynthesis via Chl esterification with FA-SOAT1/Soat1, SOAT2/Soat2, and LCAT/Lcat-were also identified.…”

Section: Discussionmentioning

confidence: 94%

“…The changes in ML profiles caused by Soat1 inactivation dramatically changed the physicochemical properties of meibum, specifically its thermotropic characteristics. Earlier, we used hot stage polarized light microscopy (HSPLM) to analyze normal and abnormal human meibum and mouse TP samples [22,23]. The same approaches have been employed in this study as well (Figure 8 and Supplementary Figure S2).…”

Section: Inactivation Of Soat1 Increased the Melting Temperature Of Mmentioning

confidence: 99%

“…Both types of lipids are known to produce a common analytical ion of dehydrated and protonated cholesterol with a theoretical m/z value of 369.3521 (a neutral loss of water for Chl and a neutral loss of FA for CE). In chosen experimental conditions, monitoring this ion provided a convenient way of detecting not only Chl itself, but also other Chl-containing compounds such as CE and Chl-OAHFA [12,21,23]. Additionally, typical adducts (such as proton, ammonia, sodium, and potassium ones) of intact lipids were also analyzed, when needed.…”

Section: Analytical Instrumentation and Proceduresmentioning

confidence: 99%

“…Unlike CE, WE do not have a particular common analytical ion, unless the focus is on their FA moieties, in which case one can monitor all WE that have a particular FA in their structure. Thus, we resorted to a tested and proven approach based on monitoring their (M + H) + adducts [10,21,23].…”

Section: Analytical Instrumentation and Proceduresmentioning

confidence: 99%

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Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

Butovich

Wilkerson

Yüksel

2021

IJMS

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Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of Soat1 ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)—cholesteryl esters (CE)—in a mouse model. ML of the Soat1-null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of Soat1+/− and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in Soat1-null mice, while Soat1+/− mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to Soat1 ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The Soat1-null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of Soat1-null mice. These findings illustrate the role of Soat1/SOAT1 in the lipid homeostasis and pathophysiology of MG.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 94%

Section: Inactivation Of Soat1 Increased the Melting Temperature Of Mmentioning

confidence: 99%

Section: Analytical Instrumentation and Proceduresmentioning

confidence: 99%

Section: Analytical Instrumentation and Proceduresmentioning

confidence: 99%

See 3 more Smart Citations

Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

Butovich

Wilkerson

Yüksel

2021

IJMS

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Branched and linear fatty acid esters of hydroxy fatty acids (FAHFA) relevant to human health

Riecan

Paluchová

Lopes

et al. 2022

Pharmacology & Therapeutics

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Genome-Wide Identification and Comparative Analysis of Elongation of Very Long-Chain Fatty Acid (Elovl) Genes in Echinoderms

Liu,

Wang,

et al. 2024

Russ J Genet

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Elongation of very long-chain fatty acid (Elovl) proteins is the critical rate-limiting enzyme that catalyzes the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs). Echinoderms are extremely important research objects in various elds, such as regeneration studies and developmental biology. However, to date, the genome-wide characterization and analysis of Elovl genes in echinoderms have not been investigated. In this study, the identi cation and analysis of Elovl genes in 10 representative echinoderms were performed using bioinformatics methods. A total of 117 Elovl genes have been found in the studied echinoderms. The phylogenetic tree showed that all Elovl genes from echinoderms can be subdivided into 6 classes, Elovl3-like class, Elovl4-like class, Elovl5-like class, Elovl6-like class, Elovl7-like class, and Elovl8-like class. Furthermore, the selection pressure analysis suggested that Elovl genes in echinoderms were mainly constrained by strong purifying selection events. In general, this study provides a molecular basis for echinoderm Elovl genes and may serve as a reference for in-depth phylogenomics.

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Physiological effects of inactivation and the roles of Elovl3 /ELOVL3 in maintaining ocular homeostasis

Cited by 8 publications

References 58 publications

Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

Branched and linear fatty acid esters of hydroxy fatty acids (FAHFA) relevant to human health

Genome-Wide Identification and Comparative Analysis of Elongation of Very Long-Chain Fatty Acid (Elovl) Genes in Echinoderms

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